Medical dressing

ABSTRACT

A medical dressing is disclosed, the medical dressing has an adhesive layer having a skin-facing surface to adhere the medical dressing to a dermal surface, wherein said adhesive layer comprises a first chemical compound incorporated within said adhesive layer, and wherein at least a portion of said skin-facing surface has a coating comprising a second chemical compound. Also disclosed is a method of manufacturing such a medical dressing.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/509,111 filed Mar. 6, 2017, which is a U.S. National PhaseApplication of International Application No. PCT/EP2015/070650, filedSep. 9, 2015, which claims priority to European Application No.14184436.5, filed Sep. 11, 2014, each of which are hereby incorporatedby reference in their entirety.

FIELD OF INVENTION

The present invention relates to a medical dressing.

BACKGROUND OF THE INVENTION

A wound caused by an injury or disease may be treated by the use of abandage or wound dressing to promote healing by preventing infection andleakage from the wound. Many known wound dressings include aself-adhering adhesive, also known as pressure-sensitive adhesive (PSA),which purpose is to adhere to the wound and/or to the skin surroundingthe wound and thus to fixate the dressing in a desirable position.Various adhesives are being used for affixing medical products on theskin, some of the most common being encompassed by the terms acrylicadhesives, silicone based adhesives and hot melt adhesives, amongothers.

In order to ensure that a medical device such as a wound dressingremains in the same position after a certain time of use, an adhesivehaving a strong adherence, e.g. an acrylic adhesive, may be used.However, in case the medical device is to be attached directly on theskin, an acrylic based adhesive increases the risk for pain and damagesto the skin when such medical device is to be removed from the skin,e.g. due to skin stripping.

In contrast to acrylic adhesives, silicone based adhesives are known inthe art to be very gentle on the skin. This is because a silicone basedadhesive is typically relatively soft and therefore it can follow thecontours of the skin well, resulting in a large contact surface areabetween the adhesive and the skin. Thus, although the actual adhesiveforce in each contact point of a silicone based adhesive is less thanthat of an acrylic adhesive, the large contact surface area achievedwith a silicone based adhesive affords a high overall adherence to theskin, whilst at the same time being skin-friendly, i.e. when a siliconebased adhesive is removed from the skin very few skin cells are removeddue to the low adhesive force in each contact point, thereby the abovementioned problem of skin stripping can be avoided.

For some type of wounds, such as for example severe burns and chronicwounds, there is a particular need to use a wound dressing that includesan antimicrobial agent to thereby eliminate or reduce the risk ofinfection of the wound. To that end, various types of antimicrobialdressings have been developed. Examples of antimicrobial agents thathave been explored for use in wound dressings include conventionalantiseptics, antibiotics, antimicrobial peptides, or metallic agentswith antimicrobial properties. For example, silver-containing compounds,such as silver salts, are commonly used in antimicrobial wounddressings.

WO2008057155 discloses silicone gel forming compositions for temporarilyadhering a medical device to a biological substrate, such as skin. Saiddisclosure teaches silicone gel compositions comprising active agents,for instance antibiotics, antiseptics, antifungals, anti-inflammatoryagents, hormones, anticancer agents, histamine blockers, beta blockers,vitamins, sedatives, analgesics, proteolytic enzymes, and peptides,which can be bound in the composition. However, the release of theactive agent from the hydrophobic adhesive matrix, i.e. the silicone gelforming composition, is typically limited as active agents are bound inthe composition.

WO 2011/129759 discloses an antimicrobial silicone gel adhesive (andwound dressing including a layer of such silicone gel adhesive)comprising at least one silver salt and at least one hydrophiliccomponent, wherein the hydrophilic component facilitates the absorbanceof moisture in the adhesive layer and thereby affording an improvedrelease of silver from the adhesive matrix.

However, there is still a need in the art to provide an improvedadherent medical dressing.

SUMMARY OF THE INVENTION

In view of the above-mentioned and other drawbacks of the prior art, ageneral object of the present invention is to provide an adherentmedical dressing, in particular to provide an adherent medical dressingcapable of achieving an instant and sustained release of a chemicalcompound, such as an antimicrobial compound, whilst maintaining apresence of a chemical compound in the dressing.

According to a first aspect of the invention, these and other objectsare achieved through a medical dressing comprising an adhesive layerhaving a skin-facing surface to adhere the medical dressing to a dermalsurface, wherein the adhesive layer comprises a first chemical compoundincorporated within said adhesive layer, and wherein at least a portionof the skin-facing surface comprises a coating comprising a secondchemical compound.

The invention is based on the realization that an improved release ofactive chemical compound(s) and/or an improved biological activity (e.g.antimicrobial and/or wound healing activity) from an adherent medicaldressing can be achieved by an adhesive layer having a skin-facingsurface comprising a coating comprising a second chemical compound,which coating is intended to be in direct contact with a wound and/orsurrounding dermal surface during use, wherein the adhesive layercomprises a first chemical compound incorporated within the adhesivelayer. Thereby, the coating on the adhesive layer provides a rapidinitial release of the second chemical compound, whilst a more slowrelease of the first chemical compound from the adhesive layer isprovided, to thereby ensure that the release thereof is maintained overa desirable period of time and/or that a biological (e.g. antimicrobial)activity therefrom is maintained over a desirable period of time.

In embodiments of the invention, the first chemical compound may be asolid dispersion within the adhesive layer. For example, the firstchemical compound may be a plurality of solid particles distributedwithin the adhesive layer.

In embodiments of the invention, the first chemical compound may be amolecular dispersion or partial molecular dispersion within the adhesivelayer.

By “molecular dispersion” should be understood isolated molecules of thechemical compound, and by “partial molecular dispersion” should beunderstood a plurality of isolated molecules as well as a plurality ofisolated clusters of molecules e.g. crystals or particles.

In embodiments of the invention, the adhesive layer may comprise asilicone based adhesive. The inventors have realized that a siliconebased adhesive is particularly suitable as chemical compounds can beincluded in a coating thereon without substantially affecting theadhesive properties of the adhesive layer whilst the chemical compoundscan be readily released therefrom.

The term “coating” should, in the context of this application, beunderstood as at least one continuous layer on a surface, or a pluralityof dots or layers, or a discontinuous cover on a surface e.g. pluralityof particles distributed on an area of a surface.

In embodiments of the invention, the coating comprising the secondchemical compound on at least a portion of the skin-facing surface ofthe adhesive layer may comprise a plurality of particles of the secondchemical compound distributed on at least a portion of the skin-facingsurface, wherein a first portion of each particle may penetrate into theadhesive layer whilst a second portion of the particle may protrude outfrom the adhesive layer.

In embodiments of the invention, the coating comprising the secondchemical compound is intended to be in direct contact with a woundand/or surrounding dermal surface, during use of the medical dressing.

In embodiments of the invention, the coating comprising the secondchemical compound on the adhesive layer may, for example, be a filmcoating comprising a composition including the second chemical compoundand a film forming or carrier chemical compound (e.g. a polymericcompound).

In embodiments of the invention, the medical dressing may furthercomprise a substrate having a first surface facing the adhesive layer,wherein the skin-facing surface of the adhesive layer faces away fromsaid first surface of said substrate.

In embodiments of the invention, the adhesive layer may be a coating onat least a portion of said first surface of the substrate, therebyfacilitating the application of the substrate of the medical dressing todesired position, for example, such that the substrate adheres to andcovers a wound. By providing a coating comprising a second chemicalcompound, such as for example an antimicrobial compound or wound healingcompound, on the skin-facing surface of the adhesive layer, the releaseof the second chemical compound can be controlled and restricted to adesired application area.

In embodiments of the invention, the medical dressing may furthercomprise a perforated film layer sandwiched between the first surface ofthe substrate and the adhesive layer, wherein the adhesive layer may bea coating on a non-perforated portion of the perforated film layer. Forexample, a top surface of a perforated film layer may be attached tofirst surface of the substrate, wherein the adhesive layer may be coatedon a bottom surface of a portion of the perforated film, and wherein thetop surface of the perforated film layer is opposite to, or faces awayfrom, the bottom surface thereof. The perforated film layer may, forexample, be a perforated polymeric film layer such as a perforatedpolyurethane film layer having a thickness of for example 10 to 150 μm.

Accordingly, the first surface of the substrate may be exposed throughthe openings of the perforated film layer, thereby facilitating theabsorption of exudate and wound fluids from the wound, and/orfacilitating the release of the first chemical compound from thesubstrate to the wound, through the openings.

By the term “attached” as used herein should be understood one physicalelement being in contact with another physical element, e.g. a firstlayer being in contact with an adjacent second layer. For example, inembodiments of the invention, the term “attached” may mean that onelayer is adhered or laminated to another layer by means of an adhesivein between the attached layers, alternatively two layers may be“attached” without direct adhesive means therebetween, for example, onelayer may be placed on top of another layer wherein the layers are heldtogether by additional surrounding layers enclosing the “attached”layers.

In embodiments of the invention, the substrate may comprise an absorbentmaterial. For example, in embodiments of the invention, the absorbentmaterial may be selected from the group consisting of polymeric foamsuch as a hydrophilic polyurethane foam, a non-woven material, fibrousmaterial such as fibrous hydrophilic polymeric material, gel formingfibers, hydrogel, a matrix containing hydrocolloids, woven and knittedfibers. Thereby, the medical dressing is capable of absorbing andretaining exudates from a wound.

As used herein, the term “hydrophilic” refers to the water-permeabilityproperty of a material or the water-attracting property of a molecule.In the context of a material with pores (such as, for example, open-cellfoams) or materials with through-holes, such a material is “hydrophilic”if the material wicks up water. In the context of a material withoutpores or any through-holes, such a material is considered “hydrophilic”if it does not resist the flow of water into or through the material.For example, hydrophilicity of a material can be tested using a watercolumn of up to one inch height exerting pressure on the material for atleast 60 minutes, at least 90 minutes, or at least 24 hours. By“resisting,” it is meant that any flow of water into or through the foamin such a test is below a detection limit for the test.

In embodiments of the invention, the substrate may comprise a layer ofhydrophilic polyurethane foam material. For example, the hydrophilicfoam may be an open-cell porous foam such an hydrophilic polyurethanefoam. The foam may for example be a polyurethane foam produced from acomposition comprising a prepolymer based on: hexamethylene diisocyante(HDI), toluene diisocyanate (TDI), or methylene diphenyl diisocyanate(MDI).

In embodiments of the invention, the substrate may be polymeric film,such as a polyurethane film. For example, the substrate may be apolyurethane film having a thickness of 10 to 150 μm, such as 10 to 100μm or 10 to 50 μm.

In embodiments of the invention, the substrate may be perforatedpolymeric film, for example a perforated polyurethane film having athickness of 10 to 150 μm, such as 10 to 100 μm or 10 to 50 μm, whereinthe adhesive layer may be a coating on a non-perforated portion thereof.

In embodiments of the invention, the substrate may be a net-like porousreinforcing layer as, for example, disclosed in U.S. Pat. No. 4,921,704,wherein the reinforcing layer is substantially completely encapsulatedby the adhesive layer. The reinforcing layer may for example be aflexible and elastically-extendible net of textile material, for examplea polyamide net.

In embodiments of the invention, the first chemical compound and/or thesecond chemical compound may be an antimicrobial compound.

In embodiments of the invention, the first chemical compound and thesecond chemical compound may independently be selected from the groupconsisting of a silver compound such as silver salt and metallic silver,biguanide salts such as polyhexamethylene biguanide (PHMB) or any saltsthereof, or polyhexamethyl guanide (PHMG) or any salts thereof, orchlorhexidine or any salts thereof, iodine, salicylic acid or any saltthereof, acetylsalicylic acid or any salt thereof, quarter ammoniumsalts such as benzethonium chloride, povidone-iodine (betadine),lactoferrin, xylitol, antimicrobial peptides such as human cationicantimicrobial protein 18 (hCAP18 or LL37), borneol, bismuth subgallate,antifungal pharmaceuticals, and antibiotics such as gentamycin,streptomycin.

In embodiments of the invention, the first chemical compound and thesecond chemical compound may independently be selected from the groupconsisting of a silver compound including e.g. a silver salt andmetallic silver; biguanide salts such as PHMB or any salts thereof, orPHMG or any salts thereof; chlorhexidine or any salts thereof; andiodine.

For example, the first chemical compound and/or the second chemicalcompound may be a silver salt such as silver sulfate (Ag₂SO₄), silversulfite (Ag₂SO₃), silver nitrate (AgNO₃), silver carbonate (AgCO₃),silver phosphate (Ag₃PO₄), silver chloride (AgCl), silver sodiumhydrogen zirconium phosphate (AlphaSan® from Milliken Chemical,Spartanburg, USA), or PHMB e.g. PHMB hydrochloride or any other saltsthereof, or chlorhexidine or any salts thereof.

For example, the first chemical compound and/or the second chemicalcompound may be a silver compound, for example a silver salt or metallicsilver.

In embodiments of the invention, the first chemical compound may bepresent in a first concentration by area of the medical dressing and thesecond chemical compound may be present in a second concentration byarea of the medical dressing, wherein the first and secondconcentrations may be different.

By varying the concentrations of the first and second chemicalcompounds, the release profile of the dressing can be tailor made fordifferent applications; i.e. different types of wounds.

In embodiments of the invention, the concentration of the first chemicalcompound may be about 5 to 3000 μg/cm², and wherein the concentration ofthe second chemical compound may be about 1 to 2500 μg/cm². For example,the concentration of the first chemical compound may be about 5 to 3000μg/cm², and wherein the concentration of the second chemical compoundmay be about 1 to 2500 μg/cm².

As used herein, the terms “about” or “approximately,” refer to, forexample, a number or percentage, generally including numbers that fallwithin a range of 5%, 10%, or 20% in either direction (plus or minus) ofthe number unless otherwise stated or otherwise evident from the context(except where such a number would be physically impossible, e.g. exceed100% of a possible value or fall below 0% of a possible value).

In embodiments of the invention, the adhesive layer may further comprisea hydrophilic component, as for example disclosed in WO 2011/129759,hereby incorporated by reference. Thereby, the release of the firstchemical compound from the adhesive layer may be adapted. Examples ofsuch hydrophilic component include, but are not limited to, mono- di-and/or polysaccharides, sugar alcohols, polyols, polyethers, polyesters,polyamides, and/or polymers comprising pendant carboxylic acid groupsand/or pendant sulphonate groups.

In embodiments of the invention, the substrate may comprise a thirdchemical compound, wherein the third chemical compound may be same asthe first and/or second chemical compound.

In embodiments of the invention, the third chemical compound may be asolid dispersion in the substrate. The third chemical compound may be asubstantially homogenous solid dispersion in the substrate. For example,the third chemical compound may be a molecular dispersion or partialmolecular dispersion in the substrate.

In embodiments of the invention, the substrate may be impregnated withthe third chemical compound. For example, the substrate may be a foamhaving an open cell structure, wherein the third chemical compound maybe present as a coating on the cell walls of the foam. For example, thesubstrate may be soaked with a solution or dispersion containing thethird chemical compound.

In embodiments of the invention, the substrate may include a pluralityof layers of the same or different materials. For example, the substratemay comprise a wound facing layer of absorbent foam material, a middlefibrous gel forming layer, and a top non-woven layer, wherein the middlelayer may be sandwiched between the wound facing layer and the toplayer. Thereby the liquid absorption properties of the medical dressingmay be adapted as desired. Further, the third chemical compound may beincorporated with all or only selected layer of the substrate to achievea desirable release from and/or activity within the substrate.

In embodiments of the invention, the medical dressing may include avapor permeable transmission layer attached to the substrate on a secondsurface thereof, the second surface being opposite to the first surfaceof the substrate. The transmission layer may typically be waterimpermeable.

According to a second aspect of the invention, the above-mentioned andother objects are achieved by a method of manufacturing a medicaldressing comprising the steps of:

-   -   providing an adhesive layer comprising a first chemical        compound; and    -   providing a coating comprising a second chemical compound on        said adhesive layer.

According to a third aspect of the invention, the above-mentioned andother objects are achieved through a medical dressing manufacturedaccording to the above-described method.

According to a forth aspect of the invention, the above-mentioned andother objects are achieved through the use of the medical dressingaccording to the invention for treating and/or preventing wounds. Forexample, the medical dressing according to the invention may be used inthe treatment of burns, scars, bacterial infections, viral infections,fungal infection, and/or for wound healing.

According to a fifth aspect of the invention, the above-mentioned andother objects are achieved through a method of treating a woundcomprising the step of providing the medical dressing according to theinvention on a wound and/or surrounding dermal surface.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects of the invention will now be shown in moredetail, with reference to the appended drawings showing an exemplaryembodiment of the invention, wherein:

FIG. 1 is a cross-sectional view of an embodiment of a medical dressingaccording to the invention; and

FIG. 1 b is an enlarged cross-sectional view of the cut out X in FIG. 1a.

FIG. 2 illustrates the released amount of silver over time for adressing according to the present invention compared to prior artdressings.

DESCRIPTION OF EXAMPLE EMBODIMENTS OF THE INVENTION

In the following description, example embodiments of the presentinvention are described with reference to the accompanying schematicdrawings.

FIG. 1 a shows an embodiment of a medical dressing 30 according to theinvention, wherein the medical dressing 30 comprises an adhesive layer 3having a skin-facing surface 6 to adhere the medical dressing to adermal surface, wherein the adhesive layer 3 comprises a first chemicalcompound distributed within the adhesive layer 3, and wherein at least aportion of the skin-facing surface 6 comprises a coating 9 comprising asecond chemical compound.

Thereby, the coating 9 on the adhesive layer provides a rapid initialrelease of the second chemical compound, whilst a more slow release ofthe first chemical compound from within the adhesive layer is providedto thereby ensure that the release of the first chemical compound ismaintained over a desirable period of time and/or that a biological(e.g. antimicrobial) activity exhibited by the first chemical compoundis maintained over a desirable period of time.

Different types of wounds pose different demands on a dressing. Forapplication on deep wounds, resulting from e.g. surgery, it may beadvantageous to provide a more prominent initial release of the secondchemical compound to facilitate early healing and avoid swelling at thewound site. For the purposes of infection prevention or remediation ofscars, a slower release may be desired.

By varying the concentrations of the first and second chemicalcompounds, the release profile of the dressing can be tailor made fordifferent applications. This allows for a more controlled release of thefirst and second chemical compounds.

As illustrated in FIG. 2 , a dressing comprising only the secondchemical compound on the surface provides for an excessive and quickrelease (FIG. 2 a ); i.e. a strong (e.g. antimicrobial) effectinitially, but the dressing material becomes depleted of the chemicalcompound quickly. This is not advantageous, since such a dressing wouldneed to be changed often. There may also be a risk of uncontrolled anddisproportionate release, which may cause toxicity at the wound site.

In contrast, a dressing comprising only the first chemical compound inthe adhesive layer (FIG. 2 b ) lacks an initial effect, but a stablerelease at a lower level is achieved. The chemical compound incorporatedin the adhesive layer is less accessible, and cannot exert the effect asrapidly or efficiently.

A dressing according to the invention allows for a synergistic effect byproviding a rapid initial release of the second chemical compound,whilst a more slow release of the first chemical compound from withinthe adhesive layer (FIG. 2 c ). This allows for a more controlledrelease profile, and thereby a strong initial, efficient as well assustained effect.

As exemplified in FIG. 1 a , the medical dressing 30 may further includea substrate 32, wherein the adhesive layer 3 may be coated on a firstsurface 33 of the substrate 32, which may, for example as depicted inFIG. 1 , be a plastic film such as a polyurethane film. For example, thesubstrate 32 may be a polyurethane film having a thickness in the rangeof from 10 to 150 μm, such as from 10 to 100 μm or from 10 to 80 μm, orfrom 10 to 50 μm. Alternatively, the substrate 32 may be a perforatedplastic film which may comprise a plurality of openings (or throughholes) (not shown in FIG. 1 a ) of any desirable size and shape, whereinthe adhesive layer is a coating on the non-perforated portions of theperforated film. The shape and size of the openings in the perforatedfilm may advantageously be adapted to achieve a desirable transport ofliquid through the perforated film, e.g. transport of wound fluids to aproximal absorbent member of the medical dressing or separate dressing(not shown in FIG. 1 a ). For example, the shape and size of theopenings in the perforated film may be adapted to achieve a desirablebreathability e.g. as determined by water vapor transmission rate.

In embodiments of the invention, the first chemical compound may be asolid dispersion within the adhesive layer. For example, the firstchemical compound may be a plurality of solid particles distributedwithin the adhesive layer.

In embodiments of the invention, the first chemical compound may be amolecular dispersion or partial molecular dispersion within the adhesivelayer.

For example, the first chemical compound may be substantiallyhomogenously mixed within matrix of the adhesive layer. For example, thefirst chemical compound, in particle form or as liquid solution orsuspension, may be added to a (non-cured) adhesive mixture which issubsequently coated on a substrate and thereafter cured.

In embodiment of the invention, the adhesive layer may further comprisean hydrophilic component which may enhance the water permeability and/orwater absorption capacity of the adhesive layer, and thereby the releaseof the first chemical compound from the adhesive layer may be furtheradapted. Examples of such hydrophilic component include, but are notlimited to, mono- di- and/or polysaccharides, sugar alcohols, polyols,polyethers, polyesters, polyamides, and/or polymers comprising pendantcarboxylic acid groups and/or pendant sulphonate groups. For example,the hydrophilic component may be a carboxymethyl cellulose (CMC),polyvinyl alcohol (PVA) or a polyethylene glycol (PEG)

In embodiments of the invention, the medical dressing 30 may alsofurther include a vapor permeable transmission layer (not shown in FIG.1 a ) that overlays a second surface 35 of the substrate 32. Thepermeable transmission layer may be a plastic film, for example,comprising or consisting of polyurethane, polyethylene, orpolypropylene. The vapor permeable transmission layer may be apolyurethane film having a thickness in the range of 10-100 μm, forexample, 10-80 μm such as 10-50 μm.

In embodiments of the invention, the adhesive layer may be a standaloneadhesive sheet (not shown) which may comprise a reinforcement layer,such as a perforated plastic film or fiber net (e.g. polyamide net),that is incorporated within the adhesive sheet to improve inter aliacohesion thereof. The adhesive layer 3 in FIG. 1 may for examplecomprise a silicone based adhesive.

In embodiments of the invention, the substrate 32 may comprise anabsorbent material. For example, such absorbent material may be selectedfrom the group consisting of a polymeric foam such as a hydrophilicpolyurethane foam, a non-woven material, fibrous material such asfibrous hydrophilic polymeric material, gel forming fibers, hydrogel, amatrix containing hydrocolloids, woven and knitted fibers.

In embodiments of the invention, the substrate 32 may comprise a layerof a hydrophilic polyurethane foam, for example, a polyurethane foamproduced from a composition comprising a prepolymer based on:hexamethylene diisocyante (HDI), toluene diisocyanate (TDI), ormethylene diphenyl diisocyanate (MDI).

For example, in embodiments of the invention, the substrate 2 may be ahydrophilic polyurethane foam.

In embodiments of the invention, the coating comprising the secondchemical compound may be in the form of particles (e.g. crystals orprecipitate) wherein at least a portion of each particle 9 penetratesinto the adhesive layer 3, whilst a second portion of the particleprotrudes up from the adhesive layer 3 above the skin-facing surface 6thereof. Thus, as the coating comprising the second chemical compound ison and/or protruding up from the adhesive layer 3, the release of thesecond chemical compound from the skin-facing surface 6 of the adhesivelayer 3 is facilitated.

In embodiments of the invention, as illustrated in FIG. 1 b , theadhesive layer 3 may comprise a skin portion 22 including the adhesivematerial of the adhesive layer 3 proximal to the skin-facing surface 6,and a non-skin portion 23 including the adhesive material proximal tothe non-skin facing surface 5 of the adhesive layer 3 being opposite tothe skin-facing surface 6, wherein the substrate portion 23 issubstantially free from the second chemical compound.

In embodiments of the invention, the coating 9 comprising the secondchemical compound on the skin-facing surface 6 of the adhesive layer 3may be a film coating further comprising a film forming or carrierchemical compound such as, for example, polyvinylpyrrolidone (PVP),carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), polyvinylalcohol (PVA) and/or hydroxypropyl cellulose (HPC). For example, in suchfilm coating the second chemical compound may be enclosed in a matrix ofthe film forming or carrier chemical compound. Thereby, the release ofthe second chemical compound may be further controlled by selecting afilm forming or carrier chemical compound having desirable properties,that is, by selecting for example a film forming or carrier chemicalcompound that has more or less solubility in an aqueous solution (e.g.wound fluid) the release of the second chemical can be adapted asdesired.

In embodiments of the invention, the adhesive layer 3 may comprise asilicone based adhesive, acrylic adhesive, or a pressure-sensitiveadhesive (PSA) holtmelt.

In embodiments of the invention, the adhesive layer 3 may be a coatinghaving a coating weight of from 20 to 300 g/m², for example from 50 to200 g/m² such as from 80 to 150 g/m².

In embodiments of the invention, the adhesive layer 3 may be a siliconebased adhesive. For example, the silicone based adhesive may be a softsilicone gel adhesive which adhesive is known for its advantageous skinfriendly properties as inter alia no or little skin is stripped off whenan adhesive layer of soft silicone gel adhesive is removed from a dermalsurface. The term “silicone gel” refers to a silicone gel that comprisesa cross-linked network including silicone of lower molecular weight. Forexample, suitable soft silicone gel adhesives can be composed of anaddition-cured RTV (Room Temperature Vulcanizing) silicone system which,after admixture, crosslinks and forms a self-adhesive elastomer. Oneexample of a commercially available RTV addition-cured silicone systemis Wacker SilGel 612 which is a two-component system, wherein thesoftness and degree of adherence of the formed elastomer can be variedby varying the proportions of the two components A:B from 1.0:0.7 to1.0:1.3. Other examples of silicone based adhesives include inter aliaNuSil MED-6340, NuSil MED3-6300 and NuSiI MED 12-6300 from NuSiITechnology, Carpinteria, Ga., USA, and Dow Corning 7-9800 from DowCorning Corporation, Midland, USA.

In embodiments of the invention, the first chemical compound and thesecond chemical compound may independently be selected from the groupconsisting of a silver compound including e.g. a silver salt andmetallic silver, biguanide salts such as polyhexamethylene biguanide(PHMB) or any salts thereof, or polyhexamethyl guanide (PHMG) or anysalts thereof, or chlorhexidine or any salts thereof, iodine, salicylicacid or any salt thereof, acetylsalicylic acid or any salt thereof,quarter ammonium salts such as benzethonium chloride, povidone-iodine(betadine), lactoferrin, xylitol, antimicrobial peptides such as humancationic antimicrobial protein 18 (also known as hCAP18 or LL37),borneol, bismuth subgallate, antifungal pharmaceuticals, and antibioticssuch as gentamycin, streptomycin.

In embodiments of the invention, the first chemical compound and thesecond chemical compound may independently be selected from the groupconsisting of a silver compound including e.g. a silver salt andmetallic silver; PHMB or any salts thereof; PHMG or any salts thereof;chlorhexidine or any salts thereof; and iodine.

For example, the first chemical compound and/or the second chemicalcompound may be a silver salt such as silver sulfate (Ag₂SO₄), silversulfite (Ag₂SO₃), silver nitrate (AgNO₃), silver carbonate (AgCO₃),silver phosphate (Ag₃PO₄), silver chloride (AgCl), silver sodiumhydrogen zirconium phosphate (AlphaSan® from Milliken Chemical,Spartanburg, USA), or PHMB e.g. PHMB hydrochloride or any other saltsthereof, or chlorhexidine or any salts thereof.

For example, in embodiments of the invention, the first chemicalcompound may be a silver compound e.g. silver salt or metallic silver,wherein the second chemical compound may be PHMB or any salts thereof.Alternatively, the first chemical compound may be PHMB or any saltthereof and second compound may be a silver compound or both the firstand second may be PHMB or any salt thereof, or both the first and secondmay be a silver compound. Alternatively, chlorhexidine or any saltsthereof may be combined with a silver compound.

In embodiments of the invention, the first chemical compound may bepresent in a first concentration by area of the medical dressing and thesecond chemical compound may be present in a second concentration byarea of the medical dressing, wherein the first and secondconcentrations are different. For example, the first concentration maytypically be higher than the second concentration.

In embodiments of the invention, the concentration of the first chemicalcompound may be about 5 to 3000 μg/cm², and wherein the concentration ofthe second chemical compound may be about 1 to 2500 μg/cm². For example,the concentration of the first chemical compound may be about 50 to 2000μg/cm², and wherein the concentration of the second chemical compoundmay be about 1 to 150 μg/cm². For example, the concentration of thefirst chemical compound may be about 1000 to 2500 μg/cm², and whereinthe concentration of the second chemical compound may be about 1 to 300μg/cm². For example, the concentration of the first chemical compoundmay be about 1500 to 2000 μg/cm², and wherein the concentration of thesecond chemical compound may be about 1 to 100 μg/cm². For example, theconcentration of the first chemical compound may be about 50 to 200μg/cm² such as 95 μg/cm², and wherein the concentration of the secondchemical compound may be about 5 to 49 μg/cm² such as 20 μg/cm².

For most wound care applications, it is desirable to incorporate alarger amount of the first chemical compound into the adhesive layer,and a smaller amount of the second chemical compound in the surfacecoating.

For example, the ratio between the second and the first concentrationmay be in the range of 1:5 to 1:100, e.g. 1:10 to 1:50.

This allows for both a strong initial, and sustained effect of the firstand second chemical compounds. The release of the first and secondchemical compounds can be maintained over a desirable period of time andthe biological activity of the chemical compounds can be maintained overa desirable period of time.

In embodiments of the invention, the first chemical compound and/or thesecond chemical compound may be a wound healing compound, wherein thefirst chemical compound and/or the second chemical compound mayindependently be selected from the group consisting of Edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one); full protein or peptides of:amelogenin, fibronectin, vitronectin, fibrinogen; arginylglycylasparticacid (RGD) peptides; betaglucan (BG) (e.g. soluble BG or oat BG), growthfactors such as platelet-derived growth factor (PDGF), epidermal growthfactor (EGF), fibroblast growth factor (FGF); cytokines such astransforming growth factor (TGF) beta 1, TGF beta 3, interleukin(IL)-10; decellularized animal tissue; and amniotic tissue.

In embodiments of the invention, the first chemical compound may be anantimicrobial compound selected from the group consisting of silvercompound including e.g. a silver salt and metallic silver; PHMB or anysalts thereof; PHMG or any salts thereof, chlorhexidine or any saltsthereof; and iodine, wherein the second chemical compound may be a woundhealing compound selected from the group consisting of Edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one); full protein or peptides of:amelogenin, fibronectin, vitronectin, fibrinogen; arginylglycylasparticacid (RGD) peptides; betaglucan (BG) (e.g. soluble BG or oat BG), growthfactors such as platelet-derived growth factor (PDGF), epidermal growthfactor (EGF), fibroblast growth factor (FGF); cytokines such astransforming growth factor (TGF) beta 1, TGF beta 3, interleukin(IL)-10; decellularized animal tissue; and amniotic tissue.

In embodiments of the invention, the substrate may comprise a thirdchemical compound, wherein the third chemical compound may be same asthe first and/or second chemical compound.

In embodiments of the invention, the third chemical compound may bedistributed within the substrate. For example, the third chemicalcompound may be substantially homogenously distributed within thesubstrate, i.e. having a uniform material composition throughout thesubstrate. For example, the third chemical compound may be asubstantially homogenous solid dispersion, such as a moleculardispersion or partial molecular dispersion, in the substrate.

In embodiments of the invention, the third chemical compound may bechemically bound to the structure or internal surface (e.g. pores) ofthe substrate 2. For example, in case the third chemical compound is anionic salt, the third chemical compound may be bound to a chargedinternal surface of the substrate. For example, the substrate maycomprise cellulose fibres having a charged side group, such as forexample carboxymethyl cellulose (CMC), wherein the third chemicalcompound may be bound to the cellulose fibres by ionic bonds.

The invention also relates to a method of manufacturing a medicaldressing 30 comprising the steps of:

-   -   providing an adhesive layer 3 comprising a first chemical        compound; and    -   providing a coating 9 comprising a second chemical compound on        the adhesive layer 3.

In embodiments of the invention, the step of providing an adhesive layer3 comprising a first chemical may include a step of adding a firstchemical compound to an uncured adhesive mixture, such as for example anuncured mixture of a silicone based adhesive, and subsequently curingthe adhesive mixture, to thereby achieve an adhesive layer 3 having thefirst chemical compound incorporated therewithin.

In embodiments of the invention, the step of providing a coatingcomprising a second chemical compound on the adhesive layer 3 mayinclude adding the second chemical compound to the skin-facing surface 6of the adhesive layer 3 in the form of a solid, e.g. a powder,alternatively, the second chemical compound may be dissolved ordispersed in a suitable solvent, e.g. water or organic solvents such asalcohol, thus a solution or suspension of the second chemical compoundmay be applied to the adhesive layer 3, in which case the methodtypically comprise a further step of drying, e.g. evaporating theliquid. In embodiments of the invention, a liquid mixture (e.g. solutionor suspension) of the second chemical compound may further comprise afilm forming or carrier chemical compound (as discussed above), therebya film coating comprising the second chemical compound and the filmforming chemical compound may be achieved. A liquid mixture (e.g.solution or suspension) of the second chemical compound may be appliedby means of, for example, a sponge applicator, a brush, or a stick, or aroller, or by spreading with a spatula, or by release by a releasesheet, or the liquid mixture may be in the form of a spray, mousse,aerosol, or foam which may be directly applied to the surface. Forexample, a liquid mixture (e.g. solution or suspension) of the secondchemical compound may typically be applied to the adhesive layer 3 byspraying the liquid mixture on the skin-facing surface 6 of the adhesivelayer 3. In embodiments of the invention, in case the second chemicalcompound is dissolved or dispersed in a solvent, the viscosity of thesolvent may be configured to thereby control the level of penetration ofthe second chemical compound into the skin-facing surface 6 of adhesivelayer 3. For example, the viscosity of a liquid mixture (e.g. solutionor suspension) of the second chemical compound may typically have arelatively low viscosity, such as for example within the range of 0.65to 500 mPas.

Where features, embodiments, or aspects of the present invention aredescribed in terms of Markush groups, a person skilled in the art willrecognize that the invention is also thereby described in terms of anyindividual member or subgroup of members of the Markush group. Theperson skilled in the art will further recognize that the invention isalso thereby described in terms of any combination of individual membersor subgroups of members of Markush groups.

Additionally, it should be noted that embodiments and features describedin the context of one of the aspects and/or embodiments of the presentinvention also apply mutatis mutandis to all the other aspects and/orembodiments of the invention.

Additionally, variations to the disclosed embodiments can be understoodand effected by the skilled person in practicing the claimed invention,from a study of the drawings, the disclosure, and the appended claims.In the claims, the word “comprising” does not exclude other elements orsteps, and the indefinite article “a” or “an” does not exclude aplurality. The mere fact that certain measures are recited in mutuallydifferent dependent claims does not indicate that a combination of thesemeasures cannot be used to advantage.

The advantages of the invention have been demonstrated in experiments.

EXAMPLES Preparation of Example Embodiments of the Invention

Materials Used:

Wacker SilGel® 612 silicone based adhesive (room temperaturevulcanization silicone; two component system) commercially availablefrom Wacker; silver sulfate (Ag₂SO₄) commercially available from AlfaAesar; CMC from Akzo Nobel, polyurethane film with a thickness of about25 μm, commercially available from Epurex.

Example 1

43.3 g Silgel 612 part B was mixed thoroughly with 11.1 g CMC. After ahomogenous mixture had been achieved, 45.6 g Silgel 612 part A was addedand the blend was mixed thoroughly. The mixed silicone with about 11%CMC was coated on a polyurethane film at a coat weight of 60 gsm andcured at 145° C. for 5 minutes. After cooling, an aqueous solution ofsilver sulfate (7.0 g/L) was prepared and subsequently substantiallyuniformly sprayed (using any suitable coating apparatus or e.g. a spraycan) on the cured silicone layer, and the sample was dried at roomtemperature for at least 24 h. The total amount sprayed was 16.4 μL/cm²giving a total amount of silver sulfate on the silicone layer of about115 μg/cm².

Example 2

42.4 g Silgel 612 part B was mixed thoroughly with 1.91 g silver sulfateand 11.1 g CMC. After a homogenous mixture had been achieved, 44.6 gSilgel 612 part A was added and the blend was mixed thoroughly. Themixed silicone with 1.91% silver sulfate and 11.1% CMC was coated on apolyurethane film at a coat weight of 60 gsm and cured at 145° C. for 5minutes. The silver concentration of the silicone coated film was about115 μg/cm².

Example 3

42.6 g Silgel 612 part B was mixed thoroughly with 1.59 g silver sulfateand 11.0 g CMC. After a homogenous mixture had been achieved, 44.8 gSilgel 612 part A was added and the blend was mixed thoroughly. Themixed silicone with 1.59% silver sulfate and 11% CMC was coated on apolyurethane film at a coat weight of 60 gsm and cured at 145° C. for 5minutes. The silicone coated film received a silver concentration ofabout 95 μg/cm². After cooling, an aqueous solution of silver sulfate(2.67 g/L) was prepared and subsequently substantially uniformly sprayed(using any suitable coating apparatus or e.g. a spray can) on the curedsilicone layer, and the sample was dried at room temperature for atleast 24 h. The total amount sprayed was 7.5 μL/cm², giving a totalamount of silver sulfate on the silicone layer of about 20 μg/cm², andthus a total amount of silver sulfate in the final product of about 115μg/cm².

Silver Release Tests

The release of silver was determined by using a shaking method. Inprinciple, the test material was submerged into a test medium for aspecified period of time at a specified temperature. Thereafter, thetest material was removed from the test medium and submerged into aanother well with fresh test medium, and further incubated for aspecific time period. This procedure was repeated for additional times.The silver concentration in the test medium exposed to the test materialwas determined by acid digestion followed by analysis by InductivelyCouples Plasma Optic Emission Spectroscopy (ICP-OES).

Method Description

Circular pieces (Ø 28 mm) of Examples 1-3 were punched in triplicate andplaced into separate wells of a 6-well plate containing 2 ml of 10%Nutrient Broth (NB) in water. The 6-well plates were incubated at 35°C.±2° C. and at 100 rpm±5 rpm for 2 hours. After incubation, thecircular pieces of Examples 1-3 were moved to new wells of 6-wellplates, containing fresh 10% NB. The new 6-well plates were incubated at35° C.±2° C. and at 100 rpm±5 rpm for additional 4 hours (6 hours intotal). This procedure was repeated additional two times with incubationperiods of 18 h (24 hours in total) and 24 hours (48 hours in total),respectively.

The silver concentration was determined in the test suspension exposedto the punched pieces. The total volume of the test suspension in thewells (approximate 2 ml) was mixed with 30 ml hydrochloric acid (32%)and 6 ml of nitric acid (65%). The mixture was heated to 70° C. for 4 hand then allowed to cool. Thereafter, the solutions were transferred to100 ml volumetric flasks and diluted. The silver concentrations in thevolumetric flasks were thereafter analyzed with Inductively CoupledPlasma Optical Emission Spectroscopy (Thermo Fisher iCAP 6000 series) atthe wavelengths 328.068 nm and 338.289 nm by using axial mode.Calibration range was 0.01-20 mg/L. Standards were prepared by addingsilver stock solutions to blank sample matrix (10% NB). Standards weretreated as samples. The results were reported as μg released silver percm².

Results and Discussion

The released amounts of silver for Examples 1-3 for every measure pointare presented in FIG. 2 . The total amount of silver released at the endof the testing (48 hours) is presented in Table 1. Values are mean ofthree samples.

TABLE 1 Total amount Relative Sample (μg Ag/cm²) amount (%) Example 168.4 86.1 Example 2 7.5 9.5 Example 3 16.5 20.8

As illustrated in FIG. 2 a , Example 1 (Ag₂SO₄ on surface) shows a veryfast and high release, with 80% of total content being released alreadywithin the first 2 hours. However, already at 6 hours, the releasedecreases rapidly down to 5%, and thereafter, the release is at 1% oftotal content or below, because most of the silver has already beenreleased and the material is depleted. A product like this has mostprobably an initial strong antimicrobial effect, but needs to be changedrelatively often. There is also a risk that an initial uncontrolledrelease can cause toxic silver concentrations in the wound, and therebydelay the wound healing.

In contrast, Example 2 (Ag₂SO₄ incorporated in adhesive layer) releasesonly 4% of the total silver content within the first 2 hours, andthereafter, the release stays at a stable level of 2% at every samplingpoint thereafter. Significantly less silver is available when located inthe silicone, compared to when it is present at the surface. After 48hours of testing, only 10 percent of total silver in the material isreleased (see Table 1), i.e. most of the added silver is not of use. Assilver is a relatively expensive chemical, it is of commercial interestthat the major part of the added silver is of use, otherwise it isthrown away at the next dressing change. On the other hand, it isreasonable to assume that the release will continue at about the samelevel for additional time points. Hence, a product with those propertieswould lack an initial antimicrobial effect, would not be cost effective,but would exert antimicrobial activity for an extended time.

Example 3 is an example embodiment according to the invention, andcomprises Ag₂SO₄ sprayed onto the surface, and incorporated in thesilicone film. The total silver of Example 3 concentration is the sameas for Example 1 and 2, i.e. 115 μg silver sulfate per cm² (80 μgAg/cm²). As illustrated in in FIG. 2 , a different release profile isobtained as compared to Examples 1 and 2. After 2 hours, 16% of thetotal silver content has been released, and thereafter, the releasestays at a range between 1-2% at every sampling point. At the end of thetest, about 21% of the total silver amount has been released, which issignificantly higher compared to Example 2. The silver on the surface iseasily available and is responsible for a relatively high initialrelease, which in turn can boost an antimicrobial effect. The silver inthe silicone is less available, but gives a stable contribution andprovides for the sustained release over time. A product according to theinvention would provide for an initial, efficient as well as sustainedantimicrobial effect.

The invention claimed is:
 1. A medical dressing comprising a substratecomprising a first chemical compound, said substrate having a firstsurface, wherein said medical dressing further comprises an adhesivelayer having a skin-facing surface to adhere said medical dressing to adermal surface, and a coating comprising a second chemical compound onat least a portion of said skin-facing surface, wherein the secondchemical compound is an antimicrobial compound or a wound healingcompound.
 2. The medical dressing according to claim 1, wherein saidfirst surface of said substrate faces said adhesive layer, and whereinsaid skin-facing surface of said adhesive layer faces away from saidfirst surface of said substrate.
 3. The medical dressing according toclaim 2, wherein said adhesive layer is a coating on at least a portionof said first surface of said substrate.
 4. The medical dressingaccording to claim 2, wherein said medical dressing further comprises aperforated film layer sandwiched between said first surface of saidsubstrate and said adhesive layer, wherein said adhesive layer is acoating on a non-perforated portion of said perforated film layer. 5.The medical dressing according to claim 1, wherein said first chemicalcompound is distributed within said substrate.
 6. The medical dressingaccording to claim 1, wherein said first surface of said substratecomprises a coating of said first chemical compound, and said adhesivelayer is a coating on at least a portion of said coating of said firstchemical compound.
 7. The medical dressing according to claim 1, whereinsaid medical dressing further comprises a vapor permeable transmissionlayer, wherein said vapor permeable transmission layer overlays a secondsurface of said substrate, said second surface being opposite to saidfirst surface of said substrate.
 8. The medical dressing according toclaim 1, wherein said adhesive layer comprises a silicone basedadhesive.
 9. The medical dressing according to claim 1, wherein saidfirst chemical compound and/or said second chemical compound is anantimicrobial compound.
 10. The medical dressing according to claim 1,wherein said first chemical compound and said second chemical compoundare independently selected from the group consisting of: a silvercompound, a biguanide salt, or polyhexamethyl guanide (PHMG) or anysalts thereof, or chlorhexidine or any salts thereof, iodine, salicylicacid or any salts thereof, acetylsalicylic acid or any salts thereof, aquarter ammonium salt, povidone-iodine (betadine), lactoferrin, xylitol,an antimicrobial peptide, borneol, bismuth subgallate, an antifungalpharmaceutical, and an antibiotic.
 11. The medical dressing according toclaim 1, wherein said first chemical compound is present in a firstconcentration by area of said medical dressing and said second chemicalcompound is present in a second concentration by area of said medicaldressing, wherein said first and second concentrations are different.12. The medical dressing according to claim 1, wherein a concentrationof said first chemical compound is about 5 to 3000 μg/cm², and wherein aconcentration of said second chemical compound is about 1 to 2500μg/cm².
 13. The medical dressing according to claim 1, wherein saidsubstrate comprises an absorbent material.
 14. The medical dressingaccording to claim 13, wherein said absorbent material is selected fromthe group consisting of a polymeric foam, a non-woven material, afibrous material, gel forming fibers, a hydrogel, a matrix containinghydrocolloids, a woven material, and knitted fibers.
 15. The medicaldressing according to claim 1, wherein said adhesive layer comprises athird chemical compound distributed within said adhesive layer, whereinsaid third chemical compound is the same as said first and/or secondchemical compound.
 16. The medical dressing according to claim 1,wherein said second chemical compound is a silver compound.
 17. Themedical dressing according to claim 1, wherein said second chemicalcompound is a silver salt.
 18. The medical dressing according to claim1, wherein said second chemical compound is a biguanide salt.
 19. Themedical dressing according to claim 1, wherein said second chemicalcompound is polyhexamethylene biguanide (PHMB) or a salt thereof.
 20. Amethod of manufacturing a medical dressing comprising the steps of:providing a substrate comprising a first chemical compound; providing anadhesive layer having a skin-facing surface to adhere said medicaldressing to a dermal surface; and coating a second chemical compound onsaid skin-facing surface of said adhesive layer.